1. Field of the Invention
The present invention relates to improved means of testing human and animal subjects for the presence of certain malignancies. More specifically, an embodiment is disclosed that permits the diagnosis of several types of leukemia related to thymus cells, malignant B lymphocytes, and myelomas.
2. Detailed Discussion of Background and Prior Art
The inventor has discovered that blood sera and other body fluids collected from mice or human subjects with certain malignancies contain certain unique double-stranded DNA molecules, which have an affinity for certain members of the group of enzymes known as DNA polymerases. These DNA molecules are absent from sera obtained from mice or human subjects who do not have these malignancies. The inventor has, with others, described this discovery and these DNAs, with related information, in a series of papers. See: Perisco and Gottlieb, DNA Polymerases of Myeloma, Nature New Biology 239: 173-76 (1972); Gottlieb, Smith, Plescia, Persico, and Nicholson, Inhibitor of DNA Polymerase, Nature 246: 480-82 (1973); Gottlieb, Smith, Plescia, Nicholson, Bowers, Pankuch, and Berkoben, An Inhibitor of DNA Polymerase, in Fundamental Aspects of Neoplasia, ch. 20, pp. 269-77 (1975); Gottlieb, Gottlieb, and Nicholson, Inhibition of DNA Polymerase by Sera, in Bibliotheca Haematologica, No. 43 (Basel 1976); Brennessel, Buhrer, and Gottlieb, Use of Insoluble Heparin for Isolation of DNA Polymerase, Analytical Biochemistry 87: 411-17 (1978); Gottlieb, Chang, Buhrer, and Brennessel, Isolation from Murine Myeloma and Leukemia Cells of a Selective Inhibitor of DNA Polymerase, Cancer Research 40: 758-70 (1980).
The two DNA molecules of principal interest herein may be termed "DNA-1" and "DNA-2". It is believed that these DNAs may play an important role in the replication of leukemic cells. It is tentatively believed that DNA-1 is derived from and associated with malignant thymus cells, while DNA-2 is derived from and associated with malignant B lymphocytes and myeloma cells. DNA-1 and DNA-2 have important common properties and are at times hereafter referred to collectively as "DNA-L." (More precisely, "DNA-L" as used herein means a DNA selected from the group consisting of DNA-1 and DNA-2.)
Both DNA-1 and DNA-2 have been demonstrated to have an affinity for R-1 DNA polymerase enzyme, which is found in certain tumors. It may be recovered from murine MOPC-21 myeloma tumor by procedures described in Analytic Biochemistry 87: 411-17 (1978), supra.
Present tests for leukemia, such as bone marrow tests, may be inconvenient and traumatic for the patient. Also, their sensitivity is limited to detecting the presence of substantial numbers of cancer cells, so that early cases of leukemia may escape detection. The procedures of this invention do not involve production of antibodies, as in the work of Bogoch, Detection of Malignant Tumor Cells, U.S. Pat. No. 4,298,590 (Nov. 3, 1981). Such laborious and indirect methods of measurement are not used herein.